Research Summary:Knowing the dimensions and connectivity of synapses is fundamental to understanding function. In the brain, more than 90% of synapses occur on dendritic spines. These tiny protrusions from the surface of dendrites measure about 1 micrometer in length. Dendritic spine structure is clearly important for normal brain function because when brain function is impaired, such as in conditions of mental retardation, epilepsy, and stroke, the dendritic spines are either gone, or have highly distorted shapes and sizes.

Our goal is to elucidate structural components involved in the cell biology of learning and memory. We study long-term potentiation (LTP) and its complement, long-term depression (LTD), in the developing and mature hippocampus because these phenomena have many of the physiological characteristics that are expected for learning and memory in the brain. Our working hypothesis is synaptic plasticity that serves to modify synapses in the creation of new memories competes with homeostatic mechanisms that serve to prevent saturation of synaptic strength and neuropathology. Our focus has been on dendritic spines because they are the major postsynaptic targets of excitatory axons throughout the brain and because their structure and composition serve both synaptic plasticity and stabilizing homeostatic mechanisms.